Reduced Gene Dosage of the Psychiatric Risk Gene Cacna1c Is Associated with Impairments in Hypothalamic–Pituitary–Adrenal Axis Activity in Rats
Abstract
1. Introduction
2. Results
2.1. Cacna1c Heterozygosity Is Associated with Decreased GR Expression in the Hypothalamus and Hippocampus
2.2. Epigenetic Changes in exon17 of Nr3c1 in the Hippocampus of Heterozygous Cacan1c Rats
2.2.1. DNA Methylation
2.2.2. Histone Modifications
2.3. Cacna1c Heterozygosity Increases Peripheral Corticosterone Levels
2.4. Increased Anxiety-Associated Behavioural Responses in Cacna1c Heterozygous Rats
3. Discussion
4. Materials and Methods
4.1. Animals
4.2. ELISA
4.3. RT-qPCR
4.4. Pyrosequencing
4.5. ChIP-qPCR
4.6. Behavioural Measures of Anxiety
4.7. Statistics
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
CBG | Corticosteroid-binding globulin |
CORT | Cortisol/corticosterone |
CRH | Corticotrophin-releasing hormone |
EPM | Elevated plus maze |
GR | Glucocorticoid receptor |
HET | Heterozygous Cacna1c rat |
HPA | Hypothalamus–pituitary–adrenal |
L-VGCC | L-type voltage-gated calcium channel |
MR | Mineralocorticoid receptor |
OF | Open field |
PFC | Prefrontal cortex |
PTSD | Post-traumatic stress disorder |
SNP | Single-nucleotide polymorphism |
References
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Moon, A.L.; Mawson, E.R.; Gasalla, P.; Wilkinson, L.S.; Dwyer, D.M.; Hall, J.; Thomas, K.L. Reduced Gene Dosage of the Psychiatric Risk Gene Cacna1c Is Associated with Impairments in Hypothalamic–Pituitary–Adrenal Axis Activity in Rats. Int. J. Mol. Sci. 2025, 26, 5547. https://doi.org/10.3390/ijms26125547
Moon AL, Mawson ER, Gasalla P, Wilkinson LS, Dwyer DM, Hall J, Thomas KL. Reduced Gene Dosage of the Psychiatric Risk Gene Cacna1c Is Associated with Impairments in Hypothalamic–Pituitary–Adrenal Axis Activity in Rats. International Journal of Molecular Sciences. 2025; 26(12):5547. https://doi.org/10.3390/ijms26125547
Chicago/Turabian StyleMoon, Anna L., Eleanor R. Mawson, Patricia Gasalla, Lawrence S. Wilkinson, Dominic M. Dwyer, Jeremy Hall, and Kerrie L. Thomas. 2025. "Reduced Gene Dosage of the Psychiatric Risk Gene Cacna1c Is Associated with Impairments in Hypothalamic–Pituitary–Adrenal Axis Activity in Rats" International Journal of Molecular Sciences 26, no. 12: 5547. https://doi.org/10.3390/ijms26125547
APA StyleMoon, A. L., Mawson, E. R., Gasalla, P., Wilkinson, L. S., Dwyer, D. M., Hall, J., & Thomas, K. L. (2025). Reduced Gene Dosage of the Psychiatric Risk Gene Cacna1c Is Associated with Impairments in Hypothalamic–Pituitary–Adrenal Axis Activity in Rats. International Journal of Molecular Sciences, 26(12), 5547. https://doi.org/10.3390/ijms26125547